2-(Di-tert-butylphosphino)biphenyl → 2-{3-[(5-Methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-amine hydrochloride (28 mg, 0.107 mmol) in 1,4-dioxane (0.8 mL) was added 2-(3-bromophenyl)ethanesulfonic acid (28.25 mg, 0.107 mmol), 2-(dit-butylphosphino)biphenyl (9.6 mg, 0.032 mmol), Tris(dibenzylidineacetone)-dipalladium (0) (9.8 mg, 0.011 mmol) and sodium t-butoxide (23.65 mg, 0.246 mmol). In a sealed reaction vessel, the mixture was heated with microwave radiation at 160° C. for 13 minutes. After cooling to room temperature, methanol (5 mL) and silica gel (1.0 g) were added to the reaction mixture, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to isocratic elution using ethyl acetate:hexanes (50:50) followed by ethyl acetate:methanol (80:20) using a Biotage silica gel cartridge (8.0 g). The appropriate fractions were combined and concentrated under reduced pressure to give 2-{3-[(5-methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid (0.029 g) as a yellow solid. 1H NMR (DMSO-d6): δ9.73 (s, 1H), 9.23 (s, 1H), 8.42 (d, J=7.5 Hz, 2H), 7.74 (s, 1H), 7.63 (dd, J=7.70 Hz, 2H), 7.49-7.07 (m, 3H), 6.86 (d, J=7.3 Hz, 1H), 2.94-2.82 (m, 2H), 2.71-2.62 (m, 2H), 2.52 (s, 3H). MS m/z 410 (M+1).

Provenance & Evidence